Generation of plasma cells and CD27-IgD- B cells during hantavirus infection is associated with distinct pathological findings

Priscilla F. Kerkman, Andy Dernstedt, Lalitha Tadala, Eva Mittler, Mirjam Dannborg, Christopher Sundling, Kimia T. Maleki, Johanna Tauriainen, Anne Tuiskunen-Bäck, Julia Wigren Byström, Pauline Ocaya, Therese Thunberg, Rohit K. Jangra, Gleyder Román-Sosa, Pablo Guardado-Calvo, Felix A. Rey, Jonas Klingström, Kartik Chandran, Andrea Puhar, Clas AhlmMattias N. E. Forsell

Research output: Contribution to journalArticlepeer-review

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Abstract

Objective
Human hantavirus infections can cause haemorrhagic fever with renal syndrome (HFRS). The pathogenic mechanisms are not fully understood, nor if they affect the humoral immune system. The objective of this study was to investigate humoral immune responses to hantavirus infection and to correlate them to the typical features of HFRS: thrombocytopenia and transient kidney dysfunction.

Methods
We performed a comprehensive characterisation of longitudinal antiviral B-cell responses of 26 hantavirus patients and combined this with paired clinical data. In addition, we measured extracellular adenosine triphosphate (ATP) and its breakdown products in circulation and performed in vitro stimulations to address its effect on B cells.

Results
We found that thrombocytopenia was correlated to an elevated frequency of plasmablasts in circulation. In contrast, kidney dysfunction was indicative of an accumulation of CD27−IgD− B cells and CD27−/low plasmablasts. Finally, we provide evidence that high levels of extracellular ATP and matrix metalloproteinase 8 can contribute to shedding of CD27 during human hantavirus infection.

Conclusion
Our findings demonstrate that thrombocytopenia and kidney dysfunction associate with distinctly different effects on the humoral immune system. Moreover, hantavirus-infected individuals have significantly elevated levels of extracellular ATP in circulation.

Original languageEnglish
Article numbere1313
Number of pages18
JournalClinical and Translational Immunology
Volume10
Issue number7
DOIs
Publication statusPublished - 12 Jul 2021
Externally publishedYes

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